Syntheses of homochiral 1,2-ferrocene-functionalized Lewis acids and acid/base pairs

We report a facile approach for the synthesis of homochiral 1,2-disubstituted ferrocene-functionalized Lewis acids and acid/base pairs. The synthesis is based on chiral induction facilitated by the ortho sulfinyl subsitutent in S-Fc{S(O)p-tol}, S-1, to obtain the key intermediate S,S_p-1,2-fc{S(O)p-tol}(BMes₂), S,S_p-2a (p-tol = C₆H₄Me-4, Mes = C₆H₂Me₃-2,4,6). Subsequent substitution of the -S(O)p-tol substituent in S,S_p-2a gives access to a range of enantiomerically pure S_p-1,2-ferrocene-functionalized Lewis acids and acid/base pairs including the first homochiral 1-phosphino-2-borylferrocene. Enantiomeric excesses (e.e.s) of >95% have typically been achieved using this methodology.     

Chiral dioxovanadium(V) Schiff base complexes of 1,2-diphenyl-1,2-diaminoethane and aromatic o-hydroxyaldehydes: Synthesis,characterization, catalytic properties and structure

A series of dioxovanadium(V) complexes of tridentate ligands obtained by monocondensation of chiral 1,2-diphenyl-1,2-diaminoethane and aromatic o-hydroxyaldehydes was synthesized. The complexes were characterized by spectroscopic methods in the solid state (IR) and in solution (UV–Vis, CD, ¹H and ⁵¹V NMR). Single crystal X-ray analysis was performed with (VO₂L · H₂O)₂, denoted as (4 · H₂O)₂, where L is (S,S)-1-amino-2-{(2′-oxido-4′,6′-dimethoxyphenyl)methylene}amino-1,2-diphenylethane. Crystal structure analysis revealed that (4 · H₂O)₂ contains oxo-bridged dimers of 4 joined with water molecules by hydrogen bonding interactions, and that two five-membered chelate rings in the dimeric molecule adopt different envelope conformations, one on the asymmetric carbon atom linked to the azomethine nitrogen and the other on the asymmetric carbon atom linked to the primary amino nitrogen. The (S,S)- and (R,R)-complexes bearing the methoxy substituent in positions 3 or 5 of the salicylidene moiety catalyze the oxidation of phenyl methyl sulfide by cumene hydroperoxide yielding the corresponding sulfoxide almost quantitatively with 34–39% enantiomeric excess.     

Stabilization of the labile metal configuration in halfsandwich complexes [CpRh(PN)Hal]X

PN ligands 3 and 4, derived from 2-diphenylphosphanylmethylpyridine 2a, were synthesized, to which in the backbone a tether to a cyclopentadiene system and for comparison an ⁱPr substituent were attached. The chiral compounds were resolved by introduction of a menthoxy substituent into the 2-position of the pyridine system and/or palladium complexes with enantiomerically pure co-ligands. The tripod ligand 3b contains three different binding sites (Cp, P, N) connected by a resolved chiral carbon atom. (S_C)-configuration of this tripod ligand enforces (R_Rh)-configuration at the metal atom in the halfsandwich rhodium complex (L_Ment,S_C,R_Rh)-7b. The opposite metal configuration is inaccessible. Substitution of the chloro ligand in (L_Ment,S_C,R_Rh)-7b by halide (Br, I) or pseudohalide (N₃, CN, SCN) ligands occurs with retention of configuration to give complexes 8b-11b. However, in the reaction of (L_Ment,S_C,R_Rh)-7b with PPh₃ the pyridine arm of the tripod ligand in compound 13b becomes detached from the metal atom. In the Cp*Rh and CpRh compounds of the bidentate PN ligands 4a and 4b both metal configurations are accessible and in complexes 14a-17a and 14b-17b they equilibrate fast. The stereochemical assignments are corroborated by 9 X-ray analyses.     

A computational study of 4-substituted biphenyls in their minimum energy conformation: twist angles, structural variation, and substituent effects

The role of electronic substituent effects in determining the twist angle of 4-substituted biphenyls and the mechanism of their propagation through the biphenyl frame have been studied by quantum chemical calculations at the HF/6-31G* and B3LYP/6-311++G** levels of theory, carried out on 41 p-Ph–C₆H₄–X molecules in their equilibrium conformation. The twist angle φ about the C–C bond connecting the two benzene rings, ca 45° in unsubstituted biphenyl, almost invariably decreases when a para substituent is present. In the majority of cases the difference ?φ = φ(X) ? φ(H) is small, less than a couple of degrees; the decrease of φ becomes substantial only when the substituent is a charged π-donor or π-acceptor. Multiple regression analysis using appropriate explanatory variables indicates a quadratic dependence of ?φ on the π-donor/acceptor ability of the substituent, and, to a lesser extent, on its field effect. The propagation of substituent effects through the biphenyl frame has been studied from the structural variation of the Ph group acting as a probe (ring B). This is best measured by a linear combination of the internal ring angles, termed S _F ^BIPH(e) . Multiple regression analysis of S _F ^BIPH(e) reveals a composite field effect, a substantial proportion of which is originated by resonance- and polarization-induced π-charges on the carbon atoms of the –C₆H₄– spacer (ring A). Extended conjugation between ring A and ring B, caused by resonance and polarization effects, gives rise to quadratic terms in the regression. The reliability of S _F ^BIPH(e) as a measure of long-range polar effects is supported by correlations with various experimental parameters.     

Discovery of benthol A and its challenging stereochemical assignment: opening up a new window for skeletal diversity of super-carbon-chain compounds

Super-carbon-chain compounds (SCCCs) are marine organic molecules featuring long polyol carbon chains with numerous stereocenters. Polyol–polyene compounds (PPCs) and ladder-frame polyethers (LFPs) are two major families. It is highly challenging to establish the absolute configurations of SCCCs. In this century, few new SCCC families have been reported. Benthol A, an aberrant SCCC, was obtained from a South China Sea benthic dinoflagellate that should belong to a new taxon. Its planar structure and absolute configuration, containing thirty-five carbon stereocenters, were unambiguously established by a combination of extensive NMR spectroscopic investigations, periodate degradation of the 1,2-diol groups, ozonolysis of the carbon–carbon double bonds, J-based configurational analysis, NOE interactions, modified Mosher''s MTPA ester method, and DFT-NMR ¹³C chemical-shift calculations aided by DP4+ statistical analysis. Benthol A displayed potent antimalarial activity against Plasmodium falciparum 3D7 parasites. This new molecule combines extraordinary structural features, particularly eight scattered ether rings on a C₇₂ backbone chain, which places it within a new SCCC family between PPCs and LFPs, herein termed polyol–polyether compounds. This suggestion was strongly supported by principal component analysis. The discovery of benthol A does not only provide new insights into the untapped biosynthetic potential of marine dinoflagellates, but also opens up a new window for skeletal diversity of SCCCs.

The discovery of benthol A, a marine natural product featuring thirty-five carbon stereocenters and eight scattered ether rings within a C₇₂ backbone chain, inaugurates a new family of super-carbon-chain compounds.     

Synthesis and resolution of an α-phenyl substituted ortho-palladated matrix

A novel ortho-palladated benzylaminate matrix bearing phenyl substituent at the α-carbon stereocenter was prepared in the racemic state by direct intramolecular palladation of tertiary diphenylmethylamine with palladium(II) acetate; its structure and palladacycle conformation were determined by ¹H NMR studies of the mononuclear triphenylphosphine adduct. The resolution of the dimeric complex was performed via recrystallization of its diastereomeric (S)-prolinate derivatives. The absolute configuration (R_C,R_C) of the enantiopure dimer thus obtained was determined by an X-ray diffraction investigation of the less soluble (R_C,S_CS_N)-diastereomer of its (S)-prolinate adduct.     

Enantioselective Michael addition of aldehydes to maleimides organocatalysed by chiral 1,2-diamines: an experimental and theoretical study

Simple and commercially available chiral 1,2-diamines were used as organocatalysts for the enantioselective conjugate addition of aldehydes, including α,α-disubstituted, to maleimides. The reaction was carried out in the presence of hexanedioic acid as an additive in aqueous solvents at room temperature. By employing (1S,2S)- and (1R,2R)-cyclohexane-1,2-diamine as organocatalysts, the corresponding Michael adducts bearing new stereocenters were obtained in high or quantitative yields with enantioselectivities of up to 92%, whereas the use of (1S,2S)-1,2-diphenylethane-1,2-diamine gave a much lower ee. Theoretical calculations were used to justify the observed sense of the stereoinduction.     

ZUR DARSTELLUNG VON BENZODITHIET-DERIVATEN DURCH THERMOLYSE 1,2-DITHIO-SUBSTITUIERTER BENZOLE

Abstract

The thermal fragmentation of various 1,2-dithio-benzene derivatives R₄C₆S₂(X) with R = H, CH₃, F in order to split off favorable leaving molecules × = Cl₂, CO or H₂C[dbnd]CH₂ and to generate the corresponding benzene-1,2-dithiete products (R₄C₆S₂), is investigated in a gas-flow reactor using real-time PE spectroscopic analysis. Results observed are: 1,2-bis(chloromercapto) benzene H₄C₆(SCl)₂ yields 1,2-benzodithiete H₄C₆S₂; none of the tetramethylated precursors fragments to the elusive tetramethyl derivative (H₃C)₄C₆S₂, but decarbonylation of tetrafluoro 1,2-benzodithio-2-on F₄C₆S₂(CO) leads to rather reactive tetrafluoro 1,2-benzodithiete F₄C₆S₂. Characteristic ionisation patterns are assigned by radical cation state comparison and by Koopmans' correlations based on MNDO eigenvalues.

Die thermische Fragmentierung verschiedenartiger 1,2-Dithiobenzol-Derivative R₄C₆S₂(X) mit R = H, CH₃, F, die unter Abspaltung günstiger Abgangsmoleküle × = Cl₂, CO oder H₂C[dbnd]CH₂ die entsprechenden Benzo-1,2-dithiet-Produkte (R₄C₆S₂) liefern konnte, wird in einem Gasdurchfluβ-Reaktor mit PE-spektroskopischer Echtzeit-Analytik untersucht. Beobachtet wird: 1,2-Bis(chloro-mercapto)benzol H₄C₆(SCl)₂ liefert 1,2-Benzodithiet; keine der tetramethylierten Ausgangsverbin-dungen fragmentiert zum vermutlich instabilen Tetramethyl-Derivat (H₃C)₄C₆S₂, aber Decar-bonylierung von Tetrafluor-1,2-benzodithio-2-co F₄C₆S₂(CO) führt zum reaktiven Tetrafluor-1,2-benzodithiet. Die charakteristischen lonisienmgsmuster werden durch Radikalkationenzustands-Vergleiche sowie durch Koopmans'-Korrelation mit MNDO-Eigenwerten zugeordnet.     

Synthesis of N-functionalized 2,2′-dipyridylamine ligands, complexation to ruthenium (II) and anchoring of complexes to papain from papaya latex

2,2′-Dipyridylamine (dpa) derivatives carrying a thiol-targeted maleimide group located at the end of an alkyl substituent on the central amine were synthesized. Reaction with the organometallic precursors [(η⁶-arene)RuCl₂]₂ (arene = benzene or p-cymene) yielded the half-sandwich cationic complexes [(η⁶-arene)Ru(dpa)Cl]⁺ where the dipyridylamine derivatives were coordinated as bidentate N,N donor ligands. Enzymatic studies showed that these derivatives were able to inactivate the cysteine endoproteinase papain by S-alkylation of the cysteine active site.     

Optically active palladacycles containing imines derived from 1-(1-naphthyl)ethylamine: new resolving agents for P-chiral phosphines

The synthesis of the new palladium metallacycles containing imines derived from 1-(1-naphthyl)ethylamine is reported. These new organometallic complexes have been used to resolve the P-chiral ligand benzylcyclohexylphenylphosphine. The absolute configuration of (R_C,S_P)-[PdCl{2-[HCN-CH(Me)C₁₀H₆]-3-ClC₆H₃}(PBzCyPh)] has been determined by single crystal X-ray analysis.     

Two-directional synthesis of the non-adjacent bis(tetrahydrofuran) core of cis-sylvaticin

Synthesis of the C₂-symmetric, non-adjacent bis(tetrahydrofuran) core of cis-sylvaticin in seven steps and 24% overall yield from (2R,3S)-1,2-epoxy-4-penten-3-ol is reported. A strategy involving assembly of the central 1,4-diol unit by silicon-tethered ring-closing metathesis and subsequent two-directional functionalization, including establishment of the cis/threo stereochemical relationships of the tetrahydrofuran rings by Sharpless asymmetric dihydroxylation/S_N2 cyclization, is employed.     

Dual thiophilic or carbophilic reactivity of N,N-dialkyl perfluorocarboxylic thioamides with organometallic reagents

N,N-dialkyl amides of perfluorothiocarboxylic acids react with organomagnesium and organolithium reagents via thiophilic or carbophilic attack of carbanion on the CS bond. The chemoselectivity depends on the nature of the organometallic species. Lithium reagents react at sulfur, with a subsequent β-elimination of fluoride, giving an N,S-ketene acetal. Simple organomagnesium reagents do not react, whereas allylmagnesium halide reacts at carbon, giving an adduct which can be trapped by methyl iodide and converted to the corresponding N,S-acetal. The latter can be transformed into a perfluoroalkyl dienamine via oxidation.     

Organometallische komplexverbindungen: VIII. Einfluss von achiralen substituenten auf die optische induktion bei der metallinduzierten synthese von 3-methyl-E-4-hexen-2-on

Bis(μ-methyl-1,3-dimethyl-η³-allylnickel) which has been modified by P ligands with a chiral substituent reacts with carbon monoxide under the formation of optically active 3-methyl-E-4-hexen-2-on. The investigated P ligands (PR^★R₂) have one chiral substituent (R^★ = 1R,3R,4S-(?)-menthyl) and the other substituents have been varied by taking the same alkyl or alkoxy groups (R = Me, Et, i-Pr, OMe, OEt, O-i-Pr). It has been found that the extent and the direction of optical induction depends on the concentration of the P-ligand and the kind of the achiral substituents at phosphorus.     

Practical resolution of an atropoisomeric α,α-disubstituted glycine with l-phenylalanine cyclohexylamide as chiral auxiliary

l-Phenylalanine cyclohexylamide has been used as a chiral auxiliary for the medium-scale resolution of 2′,1′:1,2;1″,2″:3,4-dinaphthcyclohepta-1,3-diene-6-amino-6-carboxylic acid (Bin), an α,α-disubstituted glycine with only axial dissymmetry. Coupling of X–Bin–OH (X=Ac; Bz) with H–(l)-Phe–NH–C₆H₁₁ by the EDC/HOBt method gave the dipeptide diastereoisomers X–(R)-Bin–(l)-Phe–NH–C₆H₁₁ and X–(S)-Bin–(l)-Phe–NH–C₆H₁₁, which were separated by crystallization (X=Bz) and/or chromatography. Extensive acidic hydrolysis, followed by esterification of the resulting free amino acid enantiomers, led to enantiomerically pure (−)-(R)-H–Bin–OMe and (+)-(S)-H–Bin–OMe with high yields.     

Enantioselective synthesis of C2-symmetric hexols from β,δ-diketosulfoxides

An enantioselective synthesis of (1,2S,4S,8S,10S,11)-hexahydroxyundecane, a C₂-symmetric hexol precursor of the alkaloid (−)-lythranidine, is described. This convergent synthesis was based on the stereoselective reduction of two different β,δ-diketosulfoxides.     

Experimental and DFT study of the conversion of ephedrine derivatives into oxazolidinones. Double SN2 mechanism against SN1 mechanism

Sulfonation of the N-Boc derivatives of 1,2-aminoalcohols, such as ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, thiomicamine, and chloramphenicol yields a mixture of the corresponding oxazolidinones with inversion (erythro derivatives) and/or retention of configuration (threo derivatives)at C5. We suggest a competition between two mechanisms: an intramolecular S_N2 process initiated by attack of the carbonyl oxygen of the Boc group to the benzylic carbon and the other one through a double S_N2 process. In the erythro derivatives the first mechanism is predominant, while in the threo derivatives both mechanisms have similar energy. This hypothesis is supported by theoretical calculations and additional experimental assays.     

Chiral thiophosphoramide and selenophosphoramide ligands in the Cu(I)-promoted catalytic enantioselective 1,3-dipolar cycloaddition reactions of azomethine ylides and pyrrole-2,5-dione derivatives

Chiral C₂-symmetric diphenylthiophosphoramide ligand L1 prepared from C₂-symmetric (1S,2S)-(−)-1,2-diphenylethylenediamine was found to be a fairly effective chiral ligand for Cu(I)-promoted 1,3-dipolar cycloaddition of imines and pyrrole-2,5-dione derivatives to give the corresponding adducts in moderate enantioselectivities and good yields.     

Investigations on organotin,organolead, lead(IV), and lead(II) dithiolates

Bis(triorganometal) 1,2-dithiolates (R₃M)₂S₂R′ [(HS)₂R′ = C₇H₈S₂ for toluene-dithiol-3,4 (H₂TDT); M = Sn, Pb; R = Ph; or (HS)₂R′ = C₁₀H₁₄S₂ for 1,2-dimethyl-4,5-bis(mercaptomethyl)benzene (H₂DBB); M = Sn, R = CH₃, C₆H₅; M = Pb, R = C₆H₅], diorganometal 1,2-dithiolates R₂MS₂R′ [(HS)₂R′ = C₆H₆S₂ for 1,2-dimercaptobenzene (H₂DMB); M = Pb, R = CH₃, C₂H₅, C₆H₅; or (HS)₂R′ = H₂TDT; M = Sn, R = CH₃, C₆H₅; M = Pb, R = C₆H₅; or (HS)₂R′ = H₂DBB; M = Sn, R = CH₃, C₆H₅; M = Pb, R = CH₃, C₂H₂, C₆H₅; or (HS)₂R′ = C₈H₆N₂S₂ for 2,3-dimercaptoquinoxaline (H₂QDT); M = Pb, R = C₆H₅] and some lead(IV) and lead(II) dithiolates Pb(S₂R′)_n [(HS)₂R′ = H₂DMB, n = 2; (HS)₂R′ = H₂TDT, n = 2; (HS)₂R′ = H₂DBB, n = 1 or 2] have been prepared. Vibrational, ¹H NMR, and Mössbauer spectroscopic data are consistent with pentacoordination of tin in R₂SnTDT and with tetracoordination of tin in R₂SnS₂R′ and (R₃Sn)₂S₂R′ in the solid state. The soluble compounds are monomeric in solution. Coupling constants for the methyltin compounds indicate tetracoordination in solution.     

Chiral solvating agents for carboxylic acids based on the salen moiety

A series of chiral salen C₂-symmetric aminophenols 1–4, which were derived from (1R,2R)- or (1S,2S)-1,2-diphenylethane-1,2-diamine with the corresponding salicylic aldehyde through a [2+2] condensation reaction, have been prepared. The NMR studies demonstrated that they can function as chiral solvating agents for the determination of the enantiomeric purity of chiral carboxylic acids.     

Structural variation, π-charge transfer, and transmission of electronic substituent effects in (E)-β-substituted styrenes: a quantum chemical study

The nature and transmission mechanism of substituent effects in (E)-β-substituted styrenes, C₆H₅–CH=CH–X, have been investigated from the structural changes induced by a variable substituent on the phenyl group. The molecular structures of 46 (E)-β-substituted styrenes were determined from MO calculations at the B3LYP/6-311++G** level of theory. The structural variation of the phenyl probe is best represented by two orthogonal linear combinations of the internal ring angles, S _F ^STY and S _R ^STY . Regression analysis of S _F ^STY using appropriate explanatory variables reveals a composite field effect, the main component of which originates from the long-range effect of the substituent enhanced by field-induced π-polarization of the vinylene spacer and resonance-induced field effects. The electronegativity of the substituent also plays a role in determining the value of S _F ^STY . Comparison with coplanar 4-substituted biphenyls reveals that the components of the field effect in the two molecular systems are of the same nature (apart from the electronegativity contribution, which is not present in biphenyl derivatives). However, the structural variation of the phenyl probe is more pronounced in (E)-β-substituted styrenes due to the shorter distance between substituent and probe. Analysis of π-charge distribution shows that the aptitude of the substituents to exchange π-electrons with the styrene and coplanar biphenyl frames is nearly the same. Nevertheless, the π-charge variation on the phenyl probe of (E)-β-substituted styrenes is 57 % greater than the corresponding quantity in coplanar 4-substituted biphenyls. Thus, the vinylene spacer is more effective than the phenylene spacer in transmitting π-charges. The S _R ^STY parameter is related to the amount of π-charge transferred from the –CH=CH–X moiety into the π-system of the benzene ring, or vice versa, due to the resonance effect of the variable substituent and, to a lesser extent, to field-induced π-polarization.